Anna Fagotti

Exploring PIPAC for managing platinum resistant and refractory ovarian cancer with peritoneal spread: A collaborative multi-institutional study

Platinum-resistant or refractory epithelial ovarian cancer (EOC) remains a significant clinical challenge, often leading to rapid progression and poor prognosis. Palliative treatments aimed at improving quality of life are warranted. To assess the feasibility and potential benefits of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in patients with platinum-resistant or refractory EOC. Prospective multicenter observational study (2016-2023). feasibility, defined as completion of ≥3 planned PIPAC cycles within 120 days without ≥ grade 3 treatment related adverse events (CTCAE v5.0). Secondary endpoints: safety; disease control (RECIST 1.1); changes in Peritoneal Cancer Index and Fagotti score; ascites control; CA-125 response; conversion to cytoreductive surgery (±HIPEC); and overall survival (OS). Forty patients were enrolled. Ninety-seven percent of procedures were completed. Feasibility was 65.0 % (26/40; 95 % CI 49.51-77.87); no grade ≥3 events occurred. Key secondary outcomes included a clinical benefit rate of 35 % in the intention-to-treat (ITT) population and 53.8 % in the per-protocol (PP) population, median time to ascites resolution of one cycle, and median overall survival of 14 months (17 months in PP). Higher white blood cell count and ascites volume were significantly associated with progression (p = 0.035 and p = 0.025). Three platinum-refractory patients became eligible for surgery, two underwent optimal cytoreduction. Median OS was 14 months (17 months in PP). A non-significant trend toward longer OS was observed in platinum-refractory versus platinum-resistant disease (18 vs 9 months; p = 0.093). PIPAC is a feasible, well-tolerated option in platinum-resistant and refractory EOC with potential to stabilize disease, relieve ascites and enable surgery in selected cases.

Real-life observational study on niraparib in older patients with primary tubo-ovarian cancer: a focus on safety and efficacy

Abstract Background Niraparib is approved for maintenance treatment of tubo-ovarian cancer patients, but data on older patients are limited. This retrospective study evaluated its safety and efficacy in primary advanced tubo-ovarian cancer, focusing on patients ≥ 75 years. Methods Women aged ≥ 50 years diagnosed with primary high-grade serous tubo-ovarian cancer, treated with niraparib between 2019–2023, were enrolled. Patients were stratified into three groups: A (50–64 years), B (65–74 years), and C (≥ 75 years). The primary outcome was progression-free survival. The secondary outcomes were toxicity and dose reduction. Results 127 patients were identified: 62 (48.8%) group A, 26 (20.5%) group B, and 39 (30.7%) group C. Baseline characteristics were comparable across groups, excluding a higher proportion of interval cytoreductive surgeries ( p  = 0.001), residual tumor ( p  = 0.01) and Eastern Cooperative Oncology Group (ECOG) > 1 ( p  = 0.01) in group C. Most patients started niraparib at 200 mg/day with dose reductions primarily occurred within fourth cycle. Dose reductions were observed in 77.4%, 69.2% and 56.4% of patients in groups A, B, and C, respectively ( p  = 0.08). In patients ≥ 75 years, 26 (66.7%) discontinued treatment due to disease progression (48.7%) or toxicity (17.9%). There were no significant differences in common or grade ≥ 3 adverse events between groups. Progression-free survival was 12 months (95%CI: 2.0–25.0) for group A, 29 months (95%CI: 11.0–52.0) for group B, and 16 months (95%CI: 1.0–31.0) for group C ( p  = 0.78). Conclusions Our findings suggest that niraparib is safe and well-tolerated in aged ≥ 75 years. Concerns about toxicity should not preclude the enrollment of elderly patients in treatment regiments.

Detection of Clinically Significant BRCA Large Genomic Rearrangements in FFPE Ovarian Cancer Samples: A Comparative NGS Study

Background: Copy number variations (CNVs), also referred to as large genomic rearrangements (LGRs), represent a crucial component of BRCA1/2 (BRCA) testing. Next-generation sequencing (NGS) has become an established approach for detecting LGRs by combining sequencing data with dedicated bioinformatics pipelines. However, CNV detection in formalin-fixed paraffin-embedded (FFPE) samples remains technically challenging, and there is the need to implement a robust and optimized analysis strategy for routine clinical practice. Methods: This study evaluated 40 FFPE ovarian cancer (OC) samples from patients undergoing BRCA testing. The performance of the amplicon-based NGS Diatech Myriapod® NGS BRCA1/2 panel (Diatech Pharmacogenetics, Jesi, Italy) was assessed for its ability to detect BRCA CNVs and results were compared to two hybrid capture-based reference assays. Results: Among the 40 analyzed samples (17 CNV-positive and 23 CNV-negative for BRCA genes), the Diatech pipeline showed a good concordance with the reference method—all CNVs were correctly identified in 16 cases with good enough sequencing quality. Only one result was inconclusive due to low sequencing quality. Conclusions: These findings support the clinical utility of NGS-based CNV analysis in FFPE samples when combined with appropriate bioinformatics tools. Integrating visual inspection of CNV plots with automated CNV calling improves the reliability of CNV detection and enhances the interpretation of results from tumor tissue. Accurate CNV detection directly from tumor tissue may reduce the need for additional germline testing, thus shortening turnaround times. Nevertheless, blood-based testing remains mandatory to determine whether detected BRCA CNVs are of hereditary or somatic origin, particularly in cases with a strong clinical suspicion of inherited predisposition due to young age and a personal and/or family history of OC.

Surgical timing in advanced ovarian cancer during the TRUST trial era: A systematic review, meta-analysis and study-level meta-regression of randomized controlled trials

The best surgical timing for advanced epithelial ovarian cancer, whether primary debulking surgery or interval debulking surgery, remains debated. Recent data, including the preliminary ones from TRUST trial, necessitates an updated critical evaluation. A systematic search of PubMed identified only randomized controlled trials comparing interval debulking surgery versus primary debulking surgery in patients with newly diagnosed advanced ovarian cancer. Primary outcomes included overall survival (OS) and progression-free survival (PFS). A random-effects meta-analysis, meta-regression, cumulative synthesis, and leave-one-out influence analysis were performed. A total of 2303 patients were included. Compared to primary debulking surgery, interval debulking surgery was associated with lower rates of postoperative complications (OR = 0.37; 95 % CI: 0.18-0.79; P = 0.01) and mortality (OR = 0.23; 95 % CI: 0.09-0.57; P = 0.002). Meta-analysis showed higher rates of complete cytoreduction with interval debulking surgery (OR = 3.84; 95 % CI: 2.14-6.91; P < 0.00001) and lower rates of macroscopic residual disease (OR = 0.20; 95 % CI: 0.13-0.30; P < 0.00001). Pooled data revealed no significant difference in OS (HR = 0.95; 95 % CI: 0.87-1.04; P = 0.26) or PFS (HR = 0.94; 95 % CI: 0.85-1.03; P = 0.16). Subgroup analyses by stage and residual disease confirmed similar survival outcomes. The meta-regression results suggested that even in trials with very high complete cytoreduction rates, no clinically meaningful OS benefit was observed for upfront surgery. In conclusion, interval debulking surgery offers comparable survival outcomes to primary debulking, with reduced perioperative morbidity and mortality, supporting its role as a valid surgical alternative. PROSPERO REGISTRATION NUMBER: CRD420251105308.

Platinum-rechallenge in epithelial ovarian cancer relapsing within 6 months after first-line treatment: a propensity score matching analysis

Prognosis for patients with early platinum-resistant Epithelial Ovarian Cancer (EOC) relapse after first-line chemotherapy remains poor. This study explores whether platinum rechallenge may be an option in this setting. In this retrospective, single-institute, observational study, we enrolled BRCA1/2 wild-type (BRCAwt) patients who underwent surgery (January 2017-July 2021) and relapsed within 6 months after first-line platinum-based chemotherapy. Platinum (P) rechallenge was compared with pegylated liposomal doxorubicin (PLD) or non-platinum/non-PLD therapy (weekly paclitaxel/gemcitabine/topotecan, PGT). To minimize selection bias, propensity score matching (PSM) analysis was performed. Overall, 87 patients were identified: 18 (20.7%, P cohort), 50 (57.5%, PLD cohort) and 19 (21.8%, PGT cohort); after PSM, 54/87 patients were identified with similar characteristics, 18 for each group. Grade 3/4 toxicity events were more frequent in P group patients (13/18, 72.2%), compared to PDL (5/18, 27.8%) and PGT (7/18, 38.9%)(PvsPDL: p = 0.008; PvsPGT: p = 0.044; PDLvsPGT: p = 0.479; PvsPDLvsPGT: p = 0.021). Median progression-free survival (mPFS) was 9 months (P cohort) (CI 95%; 4.842-13.158), achieving a 4-month and 3-month increase compared to PLD (mPFS 5 months, p < 0.002) and PGT group (mPFS 6 months, p < 0.05), respectively. Median overall survival (mOS) benefit was preserved: 32 months (P cohort) compared to PLD (13 months, p = 0.001) and PGT (18 months, p = 0.01) groups. On multivariate analysis, platinum rechallenge was an independent prognostic factor for PFS (HR: 0.416; 95% CI: 0.215-0.807; p = 0.009) and OS (HR: 0.175; 95% CI: 0.061-0.503; p = 0.001). Results were consistent with the whole population. Platinum rechallenge showed promising survival outcomes for BRCAwt patients recurring within 6 months after first-line platinum-based chemotherapy.

Comprehensive genomic profiling and clinico-pathologic characterization of primary ovarian leiomyosarcoma

Primary ovarian leiomyosarcomas are exceptionally rare, accounting for less than 0.1% of ovarian malignancies. Their treatment strategies remain poorly defined, and data on comprehensive genomic profiling are lacking. This study aims to characterize the pathological features and genomic landscape of primary ovarian leiomyosarcoma, highlighting similarities with uterine leiomyosarcomas based on available literature. We retrospectively analyzed 7 histologically confirmed cases of primary ovarian leiomyosarcoma diagnosed between 2013 and 2023 at a tertiary referral center. Clinical data, histopathological findings, and immunohistochemical profiles were reviewed. Genomic profiling was performed using the TruSight Oncology 500 assay, targeting 523 cancer-related genes. Only oncogenic or likely oncogenic alterations (Tier classification system I-II) were considered. All patients had International Federation of Gynecology and Obstetrics stage IA disease and underwent radical surgery. Two patients experienced pelvic recurrence; both showed increased Ki-67 and complete loss of estrogen and progesterone receptors in the relapsed tumors. Histologically, tumors exhibited spindle or epithelioid morphology with variable atypia and mitotic indices. Genomic profiling revealed a high prevalence of TP53 (71%) and PTEN (57%) alterations. Additional copy number alterations were identified in homologous recombination repair genes (BRCA2, CHEK1/2, and ATM), fibroblast growth factor (FGF) family members (FGF7/9/14), and platelet-derived growth factor receptor beta. Tumor mutational burden was low to medium in all cases, and microsatellite status was stable. Primary ovarian leiomyosarcomas exhibit a complex genomic landscape marked by genomic instability, sharing key alterations with uterine leiomyosarcomas. TP53 and PTEN mutations may play a central role in their pathogenesis. This first genomic profiling analysis of ovarian leiomyosarcomas provides a basis for further research and potential targeted therapeutic approaches in this rare malignancy.

Rethinking certainty: a retrospective study on diagnostic revisions in gynecologic pathology

Value of frozen section to tailor surgical staging in apparent early-stage epithelial ovarian cancer

Frozen section (FS) has been shown to have high accuracy in determining ovarian malignancy. However, its utility in guiding surgical approaches, particularly, lymph node staging, for early-stage epithelial ovarian cancer remains unclear. This study aimed to evaluate the post-test positive probability of FSs in identifying cases requiring lymph node or peritoneal staging. The secondary aims were sensitivity, specificity, and accuracy assessments. This retrospective study analyzed patients undergoing surgery for early-stage epithelial ovarian cancer with FS performed on ovarian masses between July 2007 and March 2023 at a tertiary center. The FS results were compared with the final histology (gold standard paraffin sections). The FS cases were categorized based on further actions as follows: lymph node staging (type A), peritoneal staging only (type B), or no additional procedures (type C). The patients were divided into group 1 (requiring lymph node and peritoneal staging) and group 2 (requiring only peritoneal staging). A comparison between specialized and general pathology diagnoses was also performed. Incorrect FS assessments were classified as under-diagnosed or over-diagnosed. Of the 715 patients, group 1 had appropriate staging in 425 of 447 cases, with 4.9% over-treatment. In group 2, staging was correct in 109 of 195 cases, with 44.1% under-treatment. For type A FSs, the post-test positive probability was 95% (95% CI 93% to 97%), with sensitivity, specificity, and accuracy rates of 76.4%, 86.1%, and 78.6%, respectively. For type B FSs, the post-test positive probability was 56% (95% CI 50% to 61%), with sensitivity, specificity, and accuracy rates of 68.6%, 84.5%, and 81%, respectively. There was no significant difference in the agreement between the specialized and general pathology groups (p = 0.92). Frozen sections suggestive of a cancer diagnosis requiring peritoneal and lymph node staging in a population with apparent early-stage epithelial ovarian cancer are highly reliable. In the case of FSs suggesting only peritoneal staging, malignancy is frequently underestimated.

Extending the timing for secondary cytoreductive surgery after second-line chemotherapy in relapsed ovarian cancer: the EXTENSION study

Relapse remains a major issue for patients with advanced epithelial ovarian cancer. Based on the DESKTOP III trial, international guidelines recommend secondary cytoreduction surgery when feasible before starting chemotherapy in platinum-sensitive relapsed ovarian cancer. Currently, neoadjuvant chemotherapy before secondary cytoreduction surgery is not advised outside of clinical trials. Recently, CHIPOR trial has shown the efficacy of secondary cytoreduction surgery with hyperthermic intra-peritoneal chemotherapy after neoadjuvant chemotherapy in an unselected population with platinum-sensitive relapsed ovarian cancer. The primary aim of this study was to assess the rate of potential delayed secondary cytoreduction surgery after 6 cycles of neoadjuvant chemotherapy. This retrospective, monocentric, observational study included patients with platinum-sensitive relapsed ovarian cancer deemed unsuitable for secondary cytoreductive surgery after evaluation by a multidisciplinary tumor board and/or diagnostic laparoscopy from January 2020 to December 2023. After 6 cycles of neoadjuvant chemotherapy, secondary cytoreduction surgery feasibility was evaluated by applying criteria for upfront secondary cytoreduction surgery in patients with at least a partial response at computed tomography scan. Overall, 522 patients with platinum-sensitive relapsed ovarian cancer were evaluated; 165 were considered unsuitable for upfront secondary cytoreduction surgery and received second-line chemotherapy. After 6 cycles of neoadjuvant chemotherapy, secondary cytoreduction surgery was considered feasible in 48 patients (29.1%, group A), while 117 patients (70.9%, group B) remained ineligible for surgery. Predictors of secondary cytoreduction surgery feasibility were analyzed. Multivariate analysis identified a favorable modeled CA125 elimination rate constant K score at second-line chemotherapy (OR 7.29, 95% CI 2.91 to 18.30, p < .001) as the only independent predictor. Patients eligible for delayed secondary cytoreduction surgery showed significantly longer progression-free survival 2 and post-relapse survival (median progression-free survival 2 12.5 vs 7.9, p < .001; median post-relapse survival: not reached vs 28.5, p = .002). In a real-life approach in a tertiary oncological center, we showed that around 30% of women with platinum-sensitive relapsed ovarian cancer, initially deemed unsuitable for secondary cytoreduction surgery, can potentially undergo delayed secondary cytoreduction surgery following a favorable response to 6 cycles of neoadjuvant chemotherapy.

Efficacy of Neoadjuvant Chemotherapy as pre-habilitation program in advanced epithelial ovarian cancer

Approximately 70 % of ovarian cancer patients present at diagnosis with advanced disease(AOC) and impaired clinical conditions, making them not ideal surgical candidates. We aimed to investigate whether neoadjuvant chemotherapy(NACT) can modify pre-operative characteristics of patients at high risk(HR) of perioperative complications, as defined in the Mayo Clinic Algorithm. We also compared their morbidity and survival outcomes with comparable HR women undergoing primary surgery (PCS). We retrospectively collected FIGO stage III and greater AOC patients undergoing either NACT-interval cytoreductive surgery(HR-NACT) or PCS from 01/2013 to 12/2022. HR features included: Albumin  1, stage IV disease, or complex surgery likely (more than hysterectomy, salpingo-oophorectomy and omentectomy). 400 patients were included. Among them, 298 met the criteria for the HR-NACT group; 203(68.1 %) underwent ICS after 3-4 cycles whislt 95(31.9 %) completed 6 NACT cycles. We reported an improvement in clinical variables in women undergoing 3-4 cycles of NACT: raise of ECOG = 0 rate(53.3 % vs 81.8 %; p < 0.001) and median albumin serum levels(3.0 g/dl vs 4.0 g/dl; p < 0.001). We identified 102 comparable HR-PCS patients. No difference in intraoperative complications was detected, while a difference was found in severe post-operative complications, favoring patients treated with both 3-4(5.4 % vs 18.6 % p = 0.0003) and 6 NACT cycles(7.8 % vs 18.6 %, p = 0.053). No difference in both DFS and OS was reported. We offer a rationale to combine non interventional pre-habilitation procedure with short term chemotherapy cycles, aiming to improve pre-operative conditions of selected HR patients.

Hyperthermic Intraperitoneal Chemotherapy in Platinum-Sensitive Recurrent Ovarian Cancer: A Randomized Trial on Survival Evaluation (HORSE; MITO-18)

PURPOSE To investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to secondary cytoreductive surgery (SCS) without neoadjuvant chemotherapy has a benefit on progression-free survival (PFS), as opposed to SCS alone in patients with platinum-sensitive recurrent epithelial ovarian cancer (platinum-free interval, &gt;6 months). METHODS This was a multicenter randomized phase III study. Random assignment was performed at the time of surgery in cases with residual tumor ≤0.25 cm. HIPEC with cisplatin (CDDP) 75 mg/m 2 for 60 minutes at 41.5°C was administered at the end of surgery in the experimental arm. Both groups received postoperative platinum-based chemotherapy. The primary end point was PFS. The safety profile and postrecurrence survival (PRS) were the secondary end points. RESULTS A total of 167 patients underwent random assignment, 82 patients to SCS plus HIPEC (experimental arm) and 85 to SCS alone (control arm). The median follow-up was 83 months (IQR, 64-102). The median PFS was 23 months (95% CI, 17 to 29) in the group that underwent surgery alone and 25 months (95% CI, 18 to 32) in the group that underwent cytoreductive surgery with HIPEC. The probability of PRS at 5 years was 61.6% (95% CI, 50.8 to 72.4) in the SCS group and 75.9% (95% CI, 66.5 to 85.3) in the SCS plus HIPEC group. The incidence of postoperative adverse events of any grade was similar between the two groups. CONCLUSION The addition of HIPEC to complete or nearly complete primary SCS did not confer a benefit in terms of PFS in patients with platinum-sensitive peritoneal recurrence.

New windows of surgical opportunity for gynecological cancers in the era of targeted therapies

Precision medicine through molecular profiling has taken a prominent role in the treatment of solid tumors and it is widely expected that this will continue to expand. With respect to gynecological cancers, a major change has particularly been observed in the treatment landscape of epithelial ovarian, endometrial, and cervical cancers. Regarding the former, maintenance therapy with either poly(ADP-ribose) polymerase inhibitors (PARPi) and/or bevacizumab has become an indispensable treatment option following the traditional combination of cytoreductive surgery and platinum-based chemotherapy. Considering endometrial cancer, the molecular classification system has now been incorporated into virtually every guideline available and molecular-directed treatment strategies are currently being researched, presumably leading to a further transformation of its treatment paradigm. After all, treatment with immune-checkpoint inhibitors that target the programmed cell death 1 (PD-1) receptor has already been shown to significantly improve disease outcomes in these patients, especially in those with mismatch repair deficient, microsatellite stability-high (MMRd-MSI-H) disease. Similarly, in recurrent/metastatic cervical cancer patients, these agents elicited improved survival rates when being added to platinum-based chemotherapy with or without bevacizumab. Interestingly, implications of these targeted therapies for surgical management have been touched on to a minor extent, but are at least as intriguing. This review therefore aims to address the wide-ranging opportunities the molecular tumor characteristics and their corresponding targeted therapies have to offer for the surgical management of epithelial ovarian, endometrial, and cervical cancers, both in the primary and recurrent setting.

Robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese)

Nearly 65% of patients with endometrial cancer who undergo primary hysterectomy have concurrent obesity. Retrospective data show advantages in using robotic surgery in these patients compared with conventional laparoscopy, namely lower conversion rate, increased rate of same-day discharge, and reduced blood loss. Nevertheless, to date no prospective randomized controlled trials have compared laparoscopic surgery versus robotic-assisted surgery in morbidly obese patients. The robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese) trial aims to find the most appropriate minimally invasive surgical approach in morbidly obese patients with endometrial carcinoma. Robotic surgery will reduce conversions to laparotomy in endometrial cancer patients with obesity compared with those who undergo surgery with conventional laparoscopy. This phase III multi-institutional study will randomize consecutive obese women with apparent early-stage endometrial cancer to either laparoscopic or robot-assisted surgery. The RObese trial will include obese (BMI≥30 kg/m Conversion rate to laparotomy between laparoscopic surgery versus robot-assisted surgery. RObese is a superiority trial. The clinical superiority margin for this study is defined as a difference in conversion rate of -6%. Assuming a significance level of 0.05 and a power of 80%, the study plans to randomize 566 patients. Patient recruitment will be completed by 2026, and follow-up will be completed by 2029 with presentation of data shortly thereafter. Two interim analyses are planned: one after the first 188 and the second after 376 randomized patients. NCT05974995.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review

PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.

Highlights from the 24th European Congress on Gynaecological Oncology in Istanbul: an ENYGO-IJGC Fellows compilation

MIRaGE (Minimally Invasive suRGery in recurrent Endometrial cancer)

Endometrial cancer is one of the most common gynecologic malignancies. Recurrence occurs in 10% to 15% of early-stage and up to 70% of advanced-stage cases. Secondary cytoreductive surgery is critical when complete gross resection is achievable. Minimally invasive surgery may offer perioperative advantages, but data on patient selection and oncologic outcomes are limited. This retrospective study included patients with first abdominal recurrence of endometrial cancer who underwent secondary cytoreductive surgery at Fondazione Policlinico Universitario A. Gemelli IRCCS between 2010 and 2023. Patients were grouped by surgical approach (minimally invasive surgery [MIS]: laparoscopy/robotic-assisted vs open surgery). The primary endpoint was the identification of clinical and radiological preoperative predictors of successful MIS, defined as complete gross resection. Secondary endpoints included intraoperative and perioperative outcomes, and survival outcomes (overall survival and progression-free survival). Among 192 patients with abdominal recurrence, 74 (38.5%) underwent MIS. The 2 groups were not fully homogeneous, differing mainly in relapse site and recurrence pattern; nevertheless, complete gross resection was achieved in 97.3% of minimally invasive procedures and 94.9% of open surgeries (p = .42). Minimally invasive surgery was associated with lower blood loss (p < .001), fewer transfusions (p = .030), shorter operative times (p < .001), and reduced hospital stays (p < .001). Independent predictors of successful MIS were body mass index ≥30, early-stage disease, single-site relapse, and loco-regional or lymph-node recurrence. No significant differences were observed in survival outcomes, with comparable overall survival (p = .47) and progression-free survival (p = .43) between groups. Minimally invasive surgery may represent a feasible option for selected patients with recurrent endometrial cancer, providing perioperative advantages with comparable survival outcomes. Prospective multicenter studies are needed to confirm oncologic safety and to refine patient selection, also in the context of integration with novel therapies.

Laparoscopic tumor load as an independent prognostic marker in advanced ovarian cancer: a 3-year cohort study

To evaluate the association between pre-operative tumor load, progression-free survival, and overall survival in patients with advanced epithelial ovarian cancer. Patients diagnosed with The International Federation of Gynecology and Obstetrics (FIGO) stage III to IV primary ovarian, tubal, or peritoneal carcinoma, who underwent intraoperative abdominal disease spread assessment using the laparoscopic predictive index value (PIV) at the Gynecologic Oncology Unit of the Policlinico-Agostino Gemelli University Hospital-IRCCS, Rome, from January 2018 to December 2020, were included. Patients were divided into 2 groups based on median laparoscopic PIV at diagnosis in our population: group A (low tumor load) with PIV from 0 to 6, group B (high tumor load), with PIV from 8 to 12, and/or with extensive miliary carcinomatosis and mesentery retraction. During the study period, 817 patients with newly diagnosed advanced epithelial ovarian cancer were included, with a median age of 60 years (range;18-87), a median CA125 level of 584 (range; 5-6262), and ascites presence in 436 cases (54.0%). With a median follow-up of 51.0 months (95% CI 49.5 to 52.5), 571 (69.9%) recurrences and 388 (47.5%) deaths were observed. The median progression-free and overall survival were 22.0 months (95% CI 19.8 to 24.2) and 53.0 months (95% CI 48.7 to 57.3), respectively. A statistically significant correlation between PIV and risk of recurrence or death was observed (p < .001). The median progression-free survival was 27 months for PIV < 8 versus 16 months for PIV ≥ 8 (p < .001). The 5-year survival rate was 54.8 % (95% CI 49.1 to 60.5) for PIV < 8 and 30.4% (95% CI 23.7 to 37.1) for PIV ≥ 8 (p < .001). This correlation was maintained in the subgroup analysis by stage. Specifically, for FIGO stage III, the 5-year survival rate was 57.2 % for the group with PIV < 8 and 26.3 % for the group with PIV ≥ 8; for FIGO stage IV, it was 47.9 % for the group with PIV < 8, and 32.8 % for the group with PIV ≥ 8. In multivariate analysis, PIV was confirmed as an independent prognostic factor for both progression-free and overall survival, along with BRCA status and residual tumor after surgery, as well as ascites for progression-free survival and age for overall survival. This study underscores tumor burden at diagnosis, quantified by PIV, as a key independent prognostic factor in advanced ovarian cancer, irrespective of FIGO stage or BRCA status, even in the era of maintenance therapies.

Role of artificial intelligence applied to ultrasound in endometrial cancer: a systematic review

To synthesize the application of artificial intelligence (AI) in ultrasound imaging for the assessment of endometrial cancer, with a focus on methodological approaches and diagnostic accuracy in predicting different outcomes. PubMed, Scopus, and Web of Science databases were searched from inception up to January 16, 2025. Studies applying AI to ultrasound imaging in the diagnosis, staging, and management of endometrial malignant pathology were included. Quality assessment of the retrieved studies was performed using the Quality Assessment Tool for Artificial Intelligence-Centered Diagnostic Test Accuracy Studies (QUADAS-AI). The protocol was registered in the PROSPERO database (registration record CRD42025648961). Thirty studies were included: 18 (60%) distinguished between benign and malignant endometrial lesions, 4 (13.3%) focused on predicting lymph node metastases, 3 (10%) evaluated myometrial invasion, and 2 (6.6%) classified tumor risk. Additionally, 2 studies assessed disease-free survival (6.6%), while another developed a model for the automated identification of endometrial lesions (3.3%). According to QUADAS-AI, most studies were at high risk of bias for subject selection (eg, sample size not specified, imaging preprocessing not performed) (27/30, 90%) and the index test (no external validation) (27/30, 90%) domains, and at low risk of bias for the reference standard (target condition correctly classified by the reference standard) (29/30, 97%) and the workflow (reasonable time between index test and reference standard) (29/30, 97%) domains. Models were externally validated in 3/30 studies (10%), internally cross-validated in 3/30 (10%), internally hold-out validated in 13/30 (43.3%), and not validated in 11/30 (36.7%). Published research on AI applications in ultrasound for endometrial cancer primarily focuses on developing classification models to distinguish benign from malignant endometrial lesions and to stage the disease. Overall, ultrasound-based AI models have demonstrated strong predictive performance. However, most studies are limited by small sample sizes and a lack of external validation.

Critical view of safety assessment in sentinel node dissection for endometrial and cervical cancer: artificial intelligence to enhance surgical safety and lymph node detection (LYSE study)

This study aims to evaluate the feasibility of video-based assessment rate of Critical Views of Safety criteria for sentinel lymph node dissection in endometrial and cervical cancer. Goal of these Critical Views of Safety is to help standardize the evaluation of surgical quality, improve the precision of sentinel lymph node identification, and lead to better patient outcomes. This international multi-center observational prospective study was conducted from April to September 2024. Surgical videos from patients with cervical and endometrial carcinoma undergoing minimally invasive sentinel lymph node dissection were collected. A total of 3 Critical Views of Safety criteria (lateral pararectal space, lateral paravesical space, internal iliac artery) were proposed based on the anatomical structures defined as mandatory to be identified before sentinel node dissection, according to previously published expert consensus. A total of 3 independent surgeons, blinded to each other's assessments, evaluated whether the proposed criteria were identifiable in the endoscopic surgical video to establish applicability (content validity) and inter-rater agreement (reliability). A total of 80 patients were enrolled, of these, 71 cases (88.8%) had videos suitable for annotation, 64 (90.1%) underwent sentinel lymph node dissection for endometrial cancer, and 7 (9.9%) for cervical cancer; the median age was 52 years (IQR 34-71) and median body mass index was 28.8 kg/m The low assessment rate of the internal iliac artery criteria should raise concerns about missing sentinel lymph nodes in the internal iliac and pre-sacral area. The assessment of such standardized safety criteria could potentially standardize the procedures, thereby improving adherence to guidelines. The introduction of the video assessment of these criteria lays the foundation for exploring the feasibility of artificial intelligence algorithms to automatically assess and document the Critical Views of Safety in surgical videos.

Molecular classification of endometrial carcinoma on endometrial biopsy: an early prognostic value to guide personalized treatment

Molecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the molecular characteristics of the tumor. This study aims to assess the feasibility of obtaining reliable molecular classification status from biopsy specimens collected during hysteroscopy to better modulate the appropriate surgical treatment. This monocentric, retrospective, observational study was conducted on 106 patients who underwent a biopsy procedure followed by radical surgery for endometrial cancer, with concurrent molecular investigation. The molecular classification was determined through immunohistochemical staining for p53 and mismatch repair proteins, along with gene sequencing for POLE. Overall, 106 patients underwent molecular investigation, which was finally achieved on 99 patients (93.4%). Among these, the molecular analysis was conducted in 71 patients (67%) on the pre-operative endometrial biopsy and on the final uterine specimen in 28 patients (26.4%). Most of the endometrial biopsies were performed using Bettocchi hysteroscopy (66%). Molecular analysis was not possible in seven patients (6.6%), with six cases due to sample inadequacy and one case attributed to intra-mucosal carcinoma. The molecular results showed that the copy number low sub-group was the most common, and five cases of 'multiple classifiers' were observed in the low-risk category. Our experience in obtaining molecular information from biopsy samples underscores the feasibility and efficacy of this technique, even in small tissue samples. This capability helps define the prognostic group of patients, facilitates timely decision-making, and develops a personalized strategy for each patient.

Risk reducing surgery with peritoneal staging in BRCA1-2 mutation carriers. A prospective study

International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO. Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected. A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed. Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.

Real-world outcomes of PARP inhibitor maintenance in advanced ovarian cancer: a focus on disease patterns and treatment modalities at recurrence

The utilization of poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) as a first-line maintenance therapy for advanced ovarian cancer has increased significantly, with ∼80% of patients potentially eligible. This expansion has led to a rise in the population experiencing platinum-sensitive recurrence, yet data on first recurrence during PARPi are limited. This real-world study from a high-volume referral center aims to elucidate recurrence rates, disease distribution, and treatment modalities at the time of progression in PARPi-treated patients. We analyzed our prospectively maintained database to identify patients receiving first-line PARPi maintenance from January 2019 to December 2022 at our institution. A total of 373 cases were identified, 51.5% of which had a BRCA mutation. With a median follow-up of 38 months, 44.8% of patients experienced recurrence, with 90.3% having a platinum-free interval exceeding 6 months. Recurrences were oligometastatic in 44.9% of cases, with BRCA mutations strongly predicting this pattern (hazard ratio 3.014, confidence interval 1.486-6.113, P = 0.002). The median progression-free survival was 39 months, significantly longer for BRCA-mutated and homologous recombination deficiency-positive patients. Over one-third of platinum-sensitive recurrent patients were candidates for local treatments, and PARPi administration was prolonged in 53.7%. Despite the notable survival improvement, a significant proportion of the population will experience a platinum-sensitive recurrence on PARPi, for which local treatments are often a viable option. Our study highlights the need for further research to determine whether the ablation of oligometastatic sites has a significant impact on post-recurrence survival and to identify if there are patient categories that would benefit from personalized follow-up due to their susceptibility to oligometastatic recurrences and local treatments.

Robotic staging for early ovarian cancer in 10 steps

Effects of niraparib dose reduction on short-term outcomes in ovarian cancer patients

Despite the individualized starting dose for maintenance therapy in ovarian cancer, the niraparib dose reduction rate remains high. The aim of this study was to evaluate the impact of niraparib dose reduction on progression-free survival in newly diagnosed primary advanced ovarian cancer and recurrent ovarian cancer patients. We also aimed to compare the reduction rates and the safety of niraparib on primary and relapse groups, and identify which factors may predict dose reduction. Patients with primary or recurrent ovarian cancer in maintenance who received niraparib between 2019 and 2022 were retrospectively evaluated. Niraparib dosing was based on individualized starting dose of 300 or 200 mg/day. The impact of niraparib dose reductions was focused on patients treated with 200 or 100 mg in both groups. Reduction rates, adverse events and predictive factors of reduction were assessed in each study group. The primary endpoint was progression-free survival in primary and relapse groups; the secondary endpoints were the reduction rates, the safety and tolerability of niraparib in both groups. Of 215 patients identified, 124 (57.7%) primary and 91 (42.3%) recurrent ovarian cancer patients were included. The majority of patients started niraparib at 200 mg/day (92.7% primary and 80.2% relapse group); dose reductions from 300 or 200 mg/day to 200 or 100 mg/day occurred more frequently within cycles 1-3 (67% primary and 45% relapse group, p=0.001). Grade≥3 adverse events were lower in the relapse group (54.8% primary and 35.1% relapse, p=0.001). In both groups, dose modifications over the treatment did not significantly impair median progression-free survival. Univariate and multivariate analysis demonstrated that weight and platinum-doublets were possible risk factors for dose reduction. Niraparib dose reduction occurs in almost half of patients within cycles 1-3, although it is significantly more common in the first-line setting. Survival outcomes seem not to be impaired by dose reduction.

Low-grade versus high-grade serous ovarian cancer: comparison of surgical outcomes after secondary cytoreductive surgery

Retrospective series have shown secondary cytoreductive surgery improves oncological outcomes in recurrent low-grade serous ovarian cancer. We aim to compare surgical procedures and complications between patients with low-grade and high-grade recurrent serous ovarian cancer. This retrospective single-institution study includes patients with recurrent low-grade and high-grade serous ovarian cancer undergoing surgery between January 2012 to December 2021. Patients were propensity matched 1:3 for residual tumor at first surgery, presence of ascites and performance status. Complexity of surgery and postoperative complications were analyzed. A total of 116 patients undergoing secondary cytoreductive surgery were included with 29 patients (25%) having low-grade ovarian cancer. The median age of the patients was 54 years (range: 19-85) and 57 years (range: 29-78) in low-grade and high-grade ovarian cancer, respectively (p=0.13). Stages III/IV at diagnosis were more frequent in patients with high-grade ovarian cancers (p<0.001). Peritoneal involvement was higher in low-grade compared with high-grade ovarian cancer as shown by the higher rate of diaphragmatic (41.4% vs 21.8%, p=0.05), abdominal wall (41.4% vs 18.4%, p=0.02) and pelvic (51.7% vs 21.8%, p=0.01) peritonectomy. Multiple bowel resections were higher in low-grade ovarian cancer (24.1% vs 8.0%, p=0.04), while high-grade ovarian cancer had a higher rate of nodal recurrences (73.2%% vs 37.9%, p=0.03). Overall, surgical complexity was higher in low-grade ovarian cancer (58.6% vs 36.8%; p=0.05), with higher median estimated blood loss (400 vs 200 mL; p=0.01) compared with high-grade. Complete cytoreduction was achieved in 26 patients (89.7%) with low-grade and 84 (96.6%) with high-grade (p=0.16) ovarian cancer, with no significant differences in postoperative complications. Secondary cytoreductive surgery in low-grade serous ovarian cancer patients was associated with higher complexity, multiple bowel resections, and higher median estimated blood loss than in high-grade serous ovarian cancer. The comparable rate of postoperative complications suggests that secondary cytoreductive surgery in this group of patients is feasible in expert centers.

Epithelial ovarian cancer and brain metastases: might the BRCA status, PARP inhibitor administration, and surgical treatment impact the survival?

To evaluate disease characteristics and survival according to This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) Eighty-five patients with ovarian cancer and brain metastasis and known

Medicolegal and insurance issues regarding BRCA1 and BRCA2 gene tests in high income countries

Hereditary breast and ovarian cancer syndrome is an autosomal dominant cancer susceptibility syndrome mainly due to variants in

The role of diagnostic laparoscopy in locally advanced cervical cancer staging

Peritoneal involvement may be overlooked in patients with locally advanced cervical cancer (LACC). This may lead to underestimation of prognosis and to undertreatment limited to locoregional disease locations. However, staging laparoscopy in LACC is not routinely performed. The primary aim of this study was to determine the proportion of peritoneal metastasis by laparoscopy and the factors associated with peritoneal metastasis in patients with LACC. Secondary aims were to evaluate the performance of staging imaging in detecting peritoneal disease and the prognosis of patients with peritoneal metastasis. Retrospective single-institution study including consecutive patients with newly diagnosed LACC (FIGO 2018 stage IB3 and IIA2-IVA) between 06/2015 and 06/2020. All women underwent PET/CT scan, MRI scan and diagnostic laparoscopy at the time of examination under anesthesia (EUA), as part of cervical cancer staging. Peritoneal metastasis was histologically confirmed in all cases. 251 patients were included. 33 (13.2 %) had peritoneal metastasis. The treatment plan was changed for 28/33 (84.8 %) patients with peritoneal metastasis (11.1 % of the entire LACC cohort). Multivariate analysis demonstrated that grade 3 (OR:1.572, 95%CI:1.021-2.419; p = 0.040) and AJCC stage T3-4 (OR:3.435, 95%CI:1.482-7.960; p = 0.004) were variables associated with increased risk of peritoneal metastasis. Sensitivity of PET/CT-scan and MRI-scan in detecting peritoneal metastasis was 4.5 % (95%CI:0.1-22.8) and 13.8 % (95%CI:3.9-31.7), respectively. Peritoneal metastasis was independently associated with worse PFS and OS (HR:3.008, 95%CI:1.779-5.087, p < 0.001 and HR:4.078, 95%CI:2.232-7.451; p < 0.001, respectively). LACC patients with grade 3 histology and/or AJCC stage T3-4 had high-risk of peritoneal metastasis and diagnostic laparoscopy might be considered as part of cervical cancer staging in these patients. Peritoneal metastasis was an independent factor associated with worse PFS and OS.

Survival outcomes in patients with BRCA mutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors

Correlation between Patients with ovarian cancer whose somatic Of 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients with Our study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients with

Extra-cranial meningioma associated with relapse of immature ovarian teratoma

Sentinel lymph node biopsy in ovarian cancer: more questions than certainties

Oregovomab: an investigational agent for the treatment of advanced ovarian cancer

PARP inhibitors in epithelial ovarian cancer: what are their potential implications for surgical management?

Role of minimally invasive secondary cytoreduction in patients with recurrent ovarian cancer

Retrospective series have shown minimally invasive secondary cytoreductive surgery is a feasible approach in selected cases of recurrent ovarian cancer. However, no predictors of minimally invasive secondary cytoreductive surgery feasibility are currently available. This study aims to identify predictive factors of minimally invasive secondary cytoreductive surgery feasibility and to compare perioperative and survival outcomes in a matched series of recurrent ovarian cancer patients who underwent secondary cytoreduction via an open or minimally invasive surgical approach. We retrospectively identified all platinum-sensitive recurrent epithelial ovarian cancer patients who underwent minimally invasive or laparotomic secondary cytoreductive surgery between January 2013 and July 2020. Each patient underwent a preoperative positron emission tomography (PET) computerized tomography (CT) scan and diagnostic laparoscopy before secondary cytoreductive surgery. A 1:2 propensity score-matched analysis was performed to balance predictive factors of minimally invasive secondary cytoreductive surgery. Overall, 276 patients were identified (62 minimally invasive and 214 open), and a complete gross resection was achieved in 262 (94.9%) patients. At multivariate analysis, predictive factors for minimally invasive secondary cytoreductive surgery were neoadjuvant chemotherapy at first diagnosis (p=0.007), site of recurrence (p=0.031), and number of lesions (p=0.001). In the 1:2 propensity-matched population (39 minimally invasive and 78 open), complete gross resection was similar for both groups (p=0.082). Early post-operative complications were significantly higher in the laparotomy (33.3%) than in the minimally invasive surgery (10.3%) group (p=0.004). Only one (2.6%) patient experienced a grade >3 early post-operative complication in the minimally invasive surgery group compared with 13 (16.7%) patients in the open cohort (p<0.001). The median follow-up period was 32 months (range: 1-92) in the propensity-matched population. The median post-recurrence survival was 81 months in the minimally invasive surgery group and was not reached in the open group (p=0.11). Patients with single or oligometastatic recurrences can be offered minimally invasive secondary cytoreductive surgery, mainly if localized in the lymph-nodes, and/or if they received neoadjuvant chemotherapy at primary diagnosis. Minimally invasive secondary cytoreductive surgery is associated with favorable perioperative outcomes with no differences in terms of post-recurrence survival with respect to open approach.

Survival associated with the use of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node metastasis in cervical cancer

Sentinel lymph node (SLN) biopsy is part of surgical treatment of apparent early-stage cervical cancer. SLN is routinely analyzed by ultrastaging and immunohistochemistry. The aim of this study was to assess the survival of patients undergoing SLN analyzed by one-step nucleic acid amplification (OSNA) compared with ultrastaging. Single-center, retrospective, cohort study. Patients undergoing primary surgery and SLN mapping ( ±pelvic lymphadenectomy) for apparent early-stage cervical cancer between May 2017 and January 2021 were included. SLN was analyzed exclusively with OSNA or with ultrastaging. Patients with bilateral SLN mapping failure, with SLN analyzed alternatively/serially with OSNA and ultrastaging, and undergoing neo-adjuvant therapy were excluded. Baseline clinic-pathological differences between the two groups were balanced with propensity-match analysis. One-hundred and fifty-seven patients were included, 50 (31.8%) in the OSNA group and 107 (68.2%) in the ultrastaging group. Median follow up time was 41 months (95%CI:37.9-42.2). 5-year DFS in patients undergoing OSNA versus ultrastaging was 87.0% versus 91.0% (p = 0.809) and 5-year overall survival was 97.9% versus 98.6% (p = 0.631), respectively. No difference in the incidence of lymph node recurrence between the two groups was noted (OSNA 20.0% versus ultrastaging 18.2%, p = 0.931). In the group of negative SLN, no 5-year DFS difference was noted between the two groups (p = 0.692). No 5-year DFS and OS difference was noted after propensity-match analysis (87.6% versus 87.0%, p = 0.726 and 97.4% versus 97.9%, p = 0.998, respectively). The use of OSNA as method to exclusively process SLN in cervical cancer was not associated with worse DFS compared to ultrastaging. Incidence of lymph node recurrence in the two groups was not different.

Transvaginal ultrasound-guided biopsy in patients with suspicious primary advanced tubo-ovarian carcinoma

To assess the accuracy of pathological diagnosis by transvaginal ultrasound-guided biopsy versus surgery in patients with suspicious primary advanced tubo-ovarian carcinoma. The Feasibility, adequacy, and safety of the procedure were also evaluated. Consecutive women with pre-operative suspicious primary advanced tubo-ovarian carcinoma presenting between July 2019 and September 2021 were enrolled. Accuracy was calculated including only cases who underwent surgery. Feasibility was defined as the number of cases in which ultrasound-guided biopsy was possible according to tumor characteristics (morphology and site). Adequacy was defined as the number of conclusive diagnoses out of the samples collected. Safety was defined by the number of major complications which were defined as hospitalization, surgery, and/or blood transfusion. A total of 278 patients were eligible for the study; 158 were enrolled, while 120 were excluded for logistic reasons or patient refusal. Ultrasound-guided biopsy was not feasible in 30 (19%) patients. The samples obtained in the remaining 128 patients were all adequate (100%), and no major complications were noted. A total of 26 (20%) patients started neoadjuvant chemotherapy on the basis of the diagnosis obtained by ultrasound, whereas 102 (80%) patients underwent surgery. Accuracy of ultrasound-guided biopsy versus surgery was 94% (96/102), with six false negative cases at ultrasound (6%). Site (prevesical peritoneum) and size (<8 mm) of the nodules resulted as major predictive factors for ultrasound-guided biopsy failure (false negative). Ultrasound-guided biopsy correctly identified 86 primary invasive tubo-ovarian carcinomas and 10 metastatic tumors. Ultrasound-guided biopsy is a feasible, safe, and accurate method to provide histological diagnosis in suspicious advanced tubo-ovarian cancer patients.

Ovarian cancer onset across different BRCA mutation types: a view to a more tailored approach for BRCA mutated patients

To evaluate the role of different specific types of germline breast cancer susceptibility This was a multicenter, international, retrospective cohort of 474 patients diagnosed with recurrent or newly diagnosed high grade serous ovarian cancer, with known germline mutations in Excluding the 29 patients with a splicing mutation, 474 patients were enrolled: 309 (65.2%) with frameshift mutations, 102 (21.5%) with nonsense mutations, and 63 (13.3%) with missense mutations. The Different types of germline

Trabectedin plus pegylated liposomal doxorubicin in patients with disease progression after PARP inhibitor maintenance: a real-life case–control study

Poly (ADP-ribose) polymerase (PARP) inhibitor resistance is problematic in epithelial ovarian cancer management and sequencing strategies may be performed to overcome this issue. In this context, our study evaluated the role of non-platinum doublet pegylated liposomal doxorubicin/trabectedin in ovarian cancer platinum-sensitive patients who experienced disease progression under PARP inhibitor maintenance. This case-control study includes patients with recurrent epithelial ovarian cancer treated between March 2016 and April 2021 who progressed under PARP inhibitor maintenance. Data of patients treated with pegylated liposomal doxorubicin/trabectedin (experimental group) were matched 1:1 with a series of patients who received platinum-based treatment (control group). The study outcomes were overall clinical benefit (including complete, partial, and stable response), progression-free survival, and overall survival. The safety of both treatments was also evaluated. A total of 26 patients in both groups were analyzed. Clinical benefit was achieved in 15 (57%) patients in the study group and 17 (65%) patients in the control group (p=0.38). Patients receiving pegylated liposomal doxorubicin/trabectedin had 5 months of progression-free survival, compared with 5 months in patients treated with platinum-based treatment (p=0.62). Patients in the experimental group achieved a median overall survival of 16 months compared with 19 months in the control group (p=0.26) There was no difference concerning severe toxicities (G3-G4) between groups, except for hepatic toxicity, which was experienced in 30% of the patients receiving pegylated liposomal doxorubicin/trabectedin and none in the control group (p<0.009). Pegylated liposomal doxorubicin/trabectedin might be an alternative option to platinum-based treatment in patients experiencing disease progression during PARP inhibitor maintenance with an acceptable toxicity profile. This might be a therapeutic option in this setting, sparing platinum compounds for subsequent relapse.

Management of ovarian masses in pregnancy: patient selection for interventional treatment

The management of pregnant women with an adnexal tumor is still challenging and in the literature few data are available. The aim of this study was to describe the management and outcome of patients with ovarian masses detected during pregnancy. As secondary aims, we evaluated the prevalence of malignancy in the International Ovarian Tumor Analysis (IOTA) morphological classes of ovarian masses diagnosed during pregnancy, and created an algorithm for the management of patients with adnexal masses during pregnancy. This was a retrospective single centered study including patients with adnexal masses detected at any trimester during pregnancy between January 2000 and December 2019. Clinical, ultrasound, surgical, and histological data were retrieved from medical records as well as information on management (ultrasound follow-up vs surgery). Indications for surgery were recorded in terms of suspicion of malignancy based on pattern recognition of the ultrasound examiner or on symptoms or prevention of complications, such as torsion, rupture, or obstacle to normal full-term pregnancy. All masses were described using IOTA terminology. A total of 113 patients were selected for the analysis. Of these, 48 (42%) patients had surveillance and 65 (58%) patients underwent surgery (11 primary ovarian tumors, one recurrence of ovarian cancer, four metastases to the ovary, 20 borderline tumors, and 29 benign lesions). Indications for surgery were suspicious malignancy in 41/65 (63.1%) cases and symptoms or prevention of complications in 24/65 (36.9%) cases. All patients in the surveillance group showed no morphological changes of the ovarian lesions at 6 months after delivery. According to the IOTA ultrasound morphological category, the prevalence of malignancy was 0% (0/37) in the unilocular cyst group, 27% (4/15) in the multilocular group, 35% (11/31) in the unilocular solid group, 70% (14/20) in the multilocular solid group, and 70% (7/10) in the solid group. Neither obstetric nor neonatal complications were reported for patients in the surveillance group or in those with benign, borderline, or primary epithelial invasive histology. In contrast, two neonatal deaths were observed in patients with ovarian choriocarcinoma and ovarian metastases. Three of the four patients with ovarian metastases died after pregnancy. IOTA ultrasound morphological classification seems useful in the characterization of ovarian masses during pregnancy. A clinical and morphological based algorithm for counseling patients has been designed.

Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850)

To investigate whether neoadjuvant chemotherapy followed by interval debulking surgery is superior to primary debulking surgery in terms of perioperative complications and progression-free survival, in advanced epithelial ovarian, fallopian tube or primary peritoneal cancer patients with high tumor load. Patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (stage IIIC-IV) underwent laparoscopy. Patients with high tumor load assessed by a standardized laparoscopic predictive index were randomly assigned (1:1 ratio) to undergo either primary debulking surgery followed by adjuvant chemotherapy (arm A), or neoadjuvant chemotherapy followed by interval debulking surgery and adjuvant chemotherapy (arm B). Co-primary outcome measures were progression-free survival and post-operative complications; secondary outcomes were overall survival, and quality of life. Survival analyses were performed on an intention-to-treat population. 171 patients were randomly assigned to primary debulking surgery (n=84) versus neoadjuvant chemotherapy (n=87). Rates of complete resection (R0) were different between the arms (47.6% in arm A vs 77.0% in arm B; p=0.001). 53 major postoperative complications were registered, mainly distributed in arm A compared with arm B (25.9% vs 7.6%; p=0.0001). All patients were included in the intent-to-treat analysis. With an overall median follow-up of 59 months (95% CI 53 to 64), 142 (83.0%) disease progressions/recurrences and 103 deaths (60.2%) occurred. Median progression-free and overall survival were 15 and 41 months for patients assigned to primary debulking surgery, compared with 14 and 43 months for patients assigned to neoadjuvant chemotherapy, respectively (HR 1.05, 95% CI 0.77 to 1.44, p=0.73; HR 1.12, 95% CI 0.76 to 1.65, p=0.56). Neoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities, but the toxicity profile is different.

Diagnostic performance of ultrasound in assessing the extension of the disease in patients with suspicion of malignant ovarian tumor: correlation between ultrasound parameters and Fagotti’s score

A radical surgical approach represents the mainstay treatment for gynecological malignancy, and preoperative staging of ovarian cancer is crucial. Ultrasound evaluation is widely recognized as the gold standard technique for the characterization of ovarian masses due to a high sensitivity for malignancy. In addition, its accuracy in defining intra-abdominal ovarian cancer spread has been previously proposed. To analyze the agreement between preoperative ultrasound examination and laparoscopic findings in assessing the extension of intra-abdominal disease using six parameters as described by Fagotti's score. When performed by expert examiners, ultrasound can be an accurate technique to assess tumor spread in ovarian cancer and therefore to predict surgical resectability. This is a single-center prospective observational study. Patients with clinical and/or radiological suspicion of advanced ovarian or peritoneal cancer will be assessed with preoperative ultrasound and assigned a score based on the six Fagotti's laparoscopic score parameters. Each parameter will then be correlated with laparoscopic findings. Eligible patients include women 18-75 years of age with clinical and/or imaging suggestive of advanced ovarian or peritoneal cancer, and an ECOG performance status 0-3. Sensitivity and specificity of ultrasound in detecting carcinomatosis, using the parameters of Fagotti's score as a reference standard. Agreement between preoperative ultrasound examination and laparoscopic findings in assessing the extension of intra-abdominal disease as described in Fagotti's score. 240 patients. The accrual started in January 2019. Enrollment should be completed approximately by October 2020 and the results will be analyzed by December 2020. The study received the Ethical Committee approval on July 19 2018 (Protocol 28967/18 ID:2172).

Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20-25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.

BRCA status assessment in epithelial ovarian cancer and the challenge of tumor testing

REPLY: SCORPION study: is it time to call primary debulking surgery superior?

ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience

Bevacizumab maintenance following platinum-based chemotherapy is an effective treatment for epithelial ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition. This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity. Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk.

Neoadjuvant chemoteraphy in unresectable ovarian cancer with olaparib and weekly carboplatin plus paclitaxel: a phase II, open label multicenter study (NUVOLA trial)

Neoadjuvant chemotherapy with interval debulking surgery represents an alternative treatment for advanced ovarian cancer. Currently, there are few data about the use of poly adenosine diphosphate-ribose polymerase inhibitors in the neoadjuvant setting. To evaluate whether the administration of olaparib in combination with standard chemotherapy in the neoadjuvant setting can improve tumor response. The addition of a poly adenosine diphosphate-ribose polymerase inhibitor to standard chemotherapy will achieve a higher response rate in BRCA mutated patients compared with standard chemotherapy TRIAL DESIGN: This is a multicenter, phase II, single arm, open label trial. Eligible patients will receive three cycles of weekly carboplatin plus paclitaxel, and intermittent olaparib administration. Responding patients will undergo an interval debulking surgery with pathological evaluation of response to chemotherapy. Patients must have histologically confirmed International Federation of Gynecology and Obstetrics stages III-IV primary ovarian, peritoneal, or fallopian tube cancers, high grade serous or endometrioid histology, not suitable for primary cytoreductive surgery with a documented BRCA1 or BRCA2 germline and/or somatic mutation. Rate of complete pathological response after three cycles of the experimental chemotherapy regimen. A total of 35 patients will be enrolled in the study. Expected complete 42 accrual in January 2022, with presentation of results by June 2022. NCT04261465.

Fertility preservation in patients with BRCA mutations or Lynch syndrome

Guidelines and expert consensus are lacking on fertility preservation in BRCA mutation carriers and in patients with Lynch syndrome. The safety of fertility preservation in this setting is still a topic of debate and multiple factors need to be carefully considered. The aim of this review was to analyze the reproductive potential of women harboring a genetic mutation affecting the DNA repair system and explore the efficacy and safety of existing fertility preservation strategies in these patients.

Minimally invasive surgical staging for early stage ovarian cancer: A long-term follow up

The standard treatment for epithelial early stage ovarian cancer (eEOC) includes laparotomic surgical staging, according to ESGO-ESMO guidelines. In the last decade, many investigators have assessed the safety and feasibility of minimally invasive surgery (MIS) staging in properly selected patients. However, survival data related to different surgical approaches (open versus MIS) are extremely limited. The aim of this study is to analyze the long-term oncological outcomes in eEOC patients treated with MIS. This is a multicenter observational retrospective study conducted in two tertiary oncological centers. We selected all consecutive women who underwent a laparoscopic or robotic staging for eEOC. From January 2008 to December 2016, 254 eEOC patients underwent a MIS staging (188 laparoscopic staging and 66 robotic staging). Overall, 18.1% of patients were upstaged due to pathological findings. A total of 203 (79.9%) patients received platinum-based adjuvant chemotherapy. After a median follow-up of 61 months (range 13-118), 39 (15.3%) patients experienced recurrence. The 5-years progression free survival (PFS) and overall survival rates were 84.0% and 93.8%, respectively. In the univariate analysis, favorable variables influencing PFS were young age (≤45 years), non-serous histotype, tumor grade 1-2, and FIGO stage IA/IB. In the multivariate analysis, only grade 3 was shown to keep its negative independent prognostic value (HR = 3.47; p = 0.004), whereas FIGO stage ≥ IC showed a trend toward significance (HR = 1.75; p = 0.099). This retrospective study represents the longest follow-up of eEOC patients managed by MIS. The MIS is a valuable therapeutic option in appropriately selected patients, although a randomized controlled trial is needed.

Rucaparib Maintenance in Upfront Ovarian Cancer: The Long-Lasting Challenge of Predicting Response to Poly (ADP-ribose) Polymerase Inhibitors

Diagnostic performance of ultrasound in assessing the extension of disease in advanced ovarian cancer

Surgical exploration remains the gold standard for evaluating the extension of disease and predicting resectability. A laparoscopy-based scoring model was developed by Fagotti and colleagues in 2006 and updated in 2015, based on the intraoperative presence or absence of some specific cancer features. The model proved an overall accuracy rate of 77% to 100% and is considered the reference test for assessing resectability in our institution. The primary aim of the study was to analyze the agreement between preoperative ultrasound examination and laparoscopic findings in assessing the extension of intraabdominal disease using 6 parameters described by Fagotti's score. This was a prospective single-center observational study. Between January 2019 and June 2020, consecutive patients with clinical or radiological suspicion of ovarian or peritoneal cancer were assessed with preoperative ultrasound examination and assigned a score based on the 6 Fagotti score parameters (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel disease). Presence of mesenteral retraction of the small bowel and miliary carcinomatosis on the serosa were also evaluated. Each parameter was correlated with laparoscopic findings. Concordance was calculated between ultrasound and laparoscopic parameters using Cohen's kappa. Cohen's kappa ranged from 0.70 to 0.90 for carcinomatosis on the small or large bowel, supracolic omentum, liver surface, and diaphragms. Cohen's kappa test was lower for carcinomatosis on the parietal peritoneum (k=0.63) and on the lesser omentum or lesser curvature of the stomach or spleen (k=0.54). The agreement between ultrasound and surgical predictive index value (score) was k=0.74. For the evaluation of mesenteral retraction and miliary carcinomatosis, the agreement was low (k=0.57 and k=0.36, respectively). The results of ultrasound and laparoscopy in the assessment of intraabdominal tumor spread were in substantial agreement for almost all the parameters. Ultrasound examination can play a useful role in the preoperative management of patients with ovarian cancer when used in dedicated referral centers.

Ovarian cancer metastases in the liver area: proposal of a standardized anatomo-surgical classification

How should randomized controlled trials in epithelial ovarian cancer be interpreted?

Nomogram to predict feasibility of minimally invasive interval debulking surgery in advanced ovarian cancer

Currently, there is no clear guidance defining the ideal candidate for minimally invasive interval debulking surgery. This study aimed to identify predictive factors for a minimally invasive approach in patients with advanced ovarian cancer who are candidates for interval debulking surgery after neoadjuvant chemotherapy. This was a single institution retrospective study conducted between January 2014 and June 2020 Perioperative variables were used to predict the likelihood of minimally invasive interval debulking surgery using multivariable models. A nomogram was developed, and internal validation was performed using the bootstrapping correction technique. This nomogram was built to visualize the effect of perioperative variables on the estimated probability of minimally invasive interval debulking surgery in patients with a clinical response after neoadjuvant chemotherapy. We used the four significant perioperative variables according to logistic regression. A total of 108 (28.4%) and 272 (71.6%) patients underwent interval debulking surgery by a minimally invasive or open approach, respectively. Absence of omental cake (odds ratio (OR) 9.15, 95% confidence interval (CI) 4.26 to 19.64, p<0.001), high volume surgeon (OR 5.43, 95% CI 2.75 to 10.71, p<0.001), less than two peritoneal sites involved (OR 2.94, 95% CI 1.34 to 6.43, p=0.007), and CA125 normalization (OR 1.79, 95% CI 1.05 to 3.36, p=0.049) correlated with the feasibility of minimally invasive interval debulking surgery at multivariate analysis. The calibration plot demonstrated good agreement between the predicted and actual probability of minimally invasive interval debulking surgery (p=0.93, Hosmer-Lemeshow test). Our nomogram may serve as a useful tool to choose the surgical approach in patients with advanced ovarian cancer undergoing interval debulking surgery.

Investigating the possible impact of peritoneal tumor exposure amongst women with early stage cervical cancer treated with minimally invasive approach

Recent findings show a detrimental impact of the minimally invasive approach on patients with early stage cervical cancer (ECC). Reasons beyond these results are unclear. The aim of the present article is to investigate the possible role of peritoneal contamination during intracorporeal colpotomy. patients with early stage cervical cancer were divided into 2 groups: no intraperitoneal exposure (N-IPE) intraperitoneal exposure (IPE) during minimally invasive surgery. Patients of the 2 groups were propensity-matched according to the major risk factors. 226 cases of the IPE group had a significant worst prognosis than the 142 cases of the N-IPE group (4.5-years disease free survival: 86.6% vs 95.9% respectively, p = 0.005), while N-IPE had similar survival to open surgery (4.5-years disease free survival: 95.0% vs 90.5% respectively, p = 0.164). Distant recurrence was more frequent among IPE patients with a borderline significance (3.5% vs 0.4% among IPE and N-IPE respectively, p = 0.083). On multivariate analysis, intraperitoneal tumor exposure was an independent prognostic factors for worse survival; patients belonging to the N-IPE group had a risk of recurrence of about 3-fold lower compared to patients of the IPE group (hazard ratio: 0.37, 95% confidence interval: 0.15-0.88, p = 0.025). it would be advisable that further prospective studies investigating the efficacy of different surgical approach in ECC take into consideration of this issue. Moreover, all other measures that could potentially prevent peritoneal exposure of tumor should be adopted during minimally invasive surgery for early stage cervical cancer to provide higher survival outcomes.

Predictive factors of surgical complications after pelvic exenteration for gynecological malignancies: a large single-institution experience

To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE). We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications. We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications. Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery.

Oncologic and obstetric outcomes after simple conization for fertility-sparing surgery in FIGO 2018 stage IB1 cervical cancer

Conization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims to provide oncologic and obstetric outcomes of a large series of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer managed by conization. Patients with early cervical cancer and a desire to preserve fertility who underwent conization and pelvic lymphadenectomy from January 1993 to December 2019 in two Italian centers were included. Inclusion criteria were: age >18 years and ≤45 years, 2018 FIGO stage IB1, no prior irradiation or chemotherapy, absence of pre-operative radiologic evidence of nodal metastases, a strong desire to preserve fertility, and absence of concomitant malignancies. We excluded patients with confirmed infertility, neuroendocrine tumor, clear cell or mucinous carcinoma. A total of 42 patients were included. The median age was 32 years (range 19-44) and median tumor size was 11 mm (range 8-20). Squamous cell carcinoma was found in 27 (64.3%). Grade 3 tumor was present in 7 (16.7%) patients and lymphovascular space involvement was detected in 15 (35.7%). At a median follow-up of 54 months (range 1-185), all patients were alive without evidence of disease. In the entire series three patients experienced recurrence resulting in an overall recurrence rate of 7.1%. All the recurrences occurred in the pelvis (2 in the cervix and 1 in the lymph nodes), resulting in a 3-year disease-free survival of 91.6%. Twenty-two (52%) patients tried to conceive; 18 pregnancies occurred in 17 patients and 12 live births were reported (6 pre-term and 6 term pregnancies). Two miscarriages were recorded, one first trimester and one second trimester fetal loss. Our study showed that conization is feasible for the conservative management of women with stage IB1 cervical cancer desiring fertility. Oncologic outcomes appear favorable in this series of patients. Future prospective studies will hopefully provide further insight into this important question.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer

To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

The potential role of systemic inflammatory markers in predicting recurrence in early-stage cervical cancer

The influence of systemic inflammatory markers on early-stage cervical cancer (ECC) patients is contradictory. No previous study analyzed whether these markers may be suggestive of recurrence. The aim of this study was to assess whether the inflammatory markers level of patients with recurrence during surveillance was different from those of patients without recurrence representing a risk factor for recurrence. Retrospective, single-center, observational study. Patients with 2009 FIGO EEC surgically treated between 2012 and 2019 were included. Baseline inflammatory markers were evaluated on the results of the complete blood count (CBC) and coagulation tests. Inflammatory markers of relapsed patients were evaluated on the last CBC performed before the relapse diagnosis. Inflammatory markers of patients with no recurrence were evaluated on the available CBC taken at the same median follow-up time as the one from relapsed patients. 174 patients were included. Baseline Systemic immune inflammation index (SII) > 663 and Systemic inflammation response index (SIRI) > 0.98 were associated with significant risk of recurrence. SII>663 and Neutrophil to lymphocyte ratio (NLR) > 2.41 were associated with increased risk of death. Significant changes between relapsed (n = 23) and non-relapsed (n = 151) patients in median values of SII (615 versus 490, p-value = 0.001), SIRI (0.74 versus 1.05, p-value = 0.005), NRL (2.95 versus 2.15, p-value = 0.0035), and MLR (0.26 versus 0.22 p-value = 0.020), showed that different levels of inflammatory markers could help identifying recurrent disease during surveillance. Baseline SII>663 and SIRI>0.98 were associated with increased risk of recurrence. Higher median values of SII, SIRI, NLR and MLR in relapsed patients highlight their potential association with recurrence.

Multimodal tumor-agnostic ctDNA analysis for minimal residual disease detection and risk stratification in ovarian cancer: results from the MITO16a/MaNGO-OV2 trial

Advanced-stage epithelial ovarian cancer (EOC) remains a therapeutic challenge due to high relapse rates and limited survival, while standard post-surgical parameters such as residual tumor (RT) incompletely capture minimal residual disease (MRD) and offer limited insight into tumor evolution. To address this gap, we investigated whether a multimodal, tumor-agnostic analysis of circulating tumor DNA (ctDNA)-integrating tumor fraction (TF) and genome-wide fragmentomic profiles (PF)-could refine early risk stratification after cytoreductive surgery and enable longitudinal monitoring during therapy. A total of 393 plasma samples from 173 patients in the phase IV MITO16a/MaNGO-OV2a trial were analyzed by shallow whole-genome sequencing at three time points: post-surgery/pre-chemotherapy (B1), post-chemotherapy (B2), and at the end of maintenance therapy or upon disease progression during maintenance (B3). Associations with progression-free survival (PFS) and overall survival (OS) were assessed using multivariable Cox models adjusted for clinical covariates. TF was detectable in 97% of patients at B1, including those classified as optimally debulked, and outperformed established clinical covariates in predicting survival [PFS: hazard ratio (HR) 1.02, P = 0.008; OS: HR 1.04, P = 0.005]. PF provided independent prognostic values (PFS: HR 1.06, P = 0.010; OS: HR 1.10, P = 0.005), and combined TF/PF modeling identified subgroups with distinct survival trajectories beyond clinical predictors (PFS: HR 1.76, P = 0.015; OS: HR 2.06, P = 0.029). Longitudinal copy number profiling revealed dynamic remodeling under treatment pressure, with recurrent 19q13.42 amplification emerging at B2 and B3. Together, these findings establish multimodal ctDNA profiling as a sensitive, non-invasive strategy for MRD detection and longitudinal surveillance in advanced EOC, refining prognostic assessment beyond clinical and surgical factors while paving the way for precision-guided therapeutic management.

Electronic nose-based volatile organic compound profiling in gynecologic oncology: current evidence and diagnostic accuracy

Volatile organic compounds profiling has emerged as a promising approach for cancer detection. Electronic noses are portable sensor-based devices capable of recognizing volatile organic compound patterns in various biological matrices, offering a rapid, non-invasive, and cost-effective diagnostic alternative. The aim of this systematic review was to evaluate the diagnostic performance of electronic noses in gynecologic oncology and to delineate their technical characteristics. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in International Prospective Register of Systematic Reviews (CRD420251122293). PubMed, Scopus, and Google Scholar were searched up to August 2025. Eligible studies included prospective investigations evaluating volatile organic compound analysis through electronic noses in ovarian, cervical, endometrial, and vulvar cancers, as well as high-grade squamous intraepithelial lesions, using histopathology as the reference standard. Diagnostic performance parameters were extracted, and the risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. No meta-analysis was performed due to study heterogeneity. Fifteen studies with a total of 1224 patients were included. Among them, 562 (45.9%) had gynecologic malignancies, and 662 (54.1%) served as controls. Ten studies (66.7%) investigated ovarian cancer, 4 (26.7%) cervical cancer, and 1 (6.7%) high-grade squamous intraepithelial lesions of the cervix; no studies evaluated endometrial or vulvar cancers. Biological matrices analyzed included breath (33.3%), urine (20%), tissue (20%), plasma (6.7%), genitourinary secretions (6.7%), or combined samples (6.7%). Reported diagnostic performance ranged from 71% to 97.7% for sensitivity, from 63% to 100% for specificity, and from 71% to 95% for accuracy across all cancer types. In ovarian cancer studies, sensitivity ranged from 71% to 97.7%, specificity from 63% to 91.4%, and accuracy from 71% to 87%. In cervical cancer studies, sensitivity ranged from 88% to 93%, and specificity from 85% to 100%. Electronic nose technologies show encouraging diagnostic accuracy in gynecologic oncology, particularly for cervical cancer, whereas performance in ovarian cancer remains more variable depending on the biological matrix and comparator group. Despite promising results, the lack of standardized protocols and the heterogeneity of current evidence limit immediate clinical translation. Larger, multicenter, and standardized studies are needed to validate their integration into diagnostic workflows.

Pelvic exenteration for vulvar cancer: contemporary outcomes from a multinational cohort study

Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

Ultrasound-based preoperative assessment for cervical cancer: a pragmatic staging and treatment-planning strategy adaptable to diverse resource settings.

Cervical cancer remains a major global health burden, particularly in low- and middle-income countries, where access to advanced imaging and treatment is often limited. While magnetic resonance imaging is considered the gold standard for loco-regional staging, recent evidence supports transvaginal/transrectal ultrasound as an accurate and cost-effective alternative when performed by trained sonographers and clinicians. Its portability and affordability make ultrasound particularly valuable in resource-constrained settings. In this paper, we present a pragmatic diagnostic and clinical strategy for managing cervical cancer in contexts where magnetic resonance imaging, sentinel lymph node mapping, and radiotherapy are not available. Building on a structured checklist of ultrasound-based parameters, we propose simple, tailored pathways to guide decisions regarding upfront surgery, neoadjuvant chemotherapy, pelvic exenteration, or palliative chemotherapy and supportive care. The approach emphasizes accurate staging through transvaginal/transrectal ultrasound combined with transabdominal scanning, allowing identification of tumor size, local extension, lymph node status, and clear contraindications to surgery. By promoting ultrasound as a reliable tool for loco-regional staging and treatment planning, we aim to improve access to cervical cancer care in low- and middle-income countries and to lay the groundwork for future prospective multi-center studies.

Homologous recombination repair status in advanced endometrial cancer: an exploratory biomarker analysis from the randomized, phase II MITOEND 3 trial

Poly (ADP-ribose) polymerase (PARP) inhibitor use in endometrial cancer (EC) requires predictive biomarkers, currently lacking in clinical practice. This study assessed the incidence of homologous recombination deficiency (HRD) using genomic loss of heterozygosity (gLOH) and a machine learning-based HRD scar signature (HRDsig). MITO END 3 was a multicenter, phase II trial of advanced EC patients randomly assigned to receive platinum-based chemotherapy ± avelumab. Of 125 patients, 102 had tumor samples available for sequencing with FoundationOne®CDx. HRD was evaluated using gLOH (cut-off ≥16%, based on ARIEL3) and HRDsig (cut-off ≥0.7, validated pan-cancer). Among 102 evaluable samples, 5 were HRDsig-positive, 90 HRDsig-negative, and 7 HRDsig unknown. gLOH was high in 10 cases, low in 53, and not assessable in 39. Most HRDsig-positive (4/5) and gLOH-high (8/10) tumors were of endometrioid histology and carried TP53 mutations. None were microsatellite instability-high. A small subgroup of advanced EC patients shows HRD positivity by gLOH or HRDsig, potentially identifying those most likely to benefit from PARP inhibitors. These tumors are typically endometrioid with TP53 mutations.

PARPi and myeloid neoplasms; the Italian MITO-MaNGO experience based on a multicentric survey

The introduction of poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer has raised increasing concerns about PARPi-related myeloid neoplasms (PrMN). Therapy-related neoplasms, including myelodysplastic syndromes and acute myeloid leukemia, account for 10%-20% of cases. Expanding PARPi indications, longer survival, and aging populations may contribute to rising PrMN incidence. Randomized clinical trials and real-world analyses show a significant risk increase, but data on individual PARPi, treatment lines, and prior therapies are limited. We evaluated PrMN incidence across 17 Italian centers using a 71-item survey distributed to MITO (Multicenter Italian Trials on Ovarian cancer) and MaNGO (Mario Negri Gynecologic Oncology) centers, focusing on patients treated with PARPi outside clinical trials. Of 2320 patients (1254 BRCA-mutated), 56 (2.55%) developed MN: 35 myelodysplastic syndromes and 21 acute myeloid leukemia (2 patients had both, counted once). Among them, 31 had BRCA mutations (2.5%). Incidence by drug was: olaparib 2.5%, niraparib 2%, and rucaparib 3.4%. An unclear correlation emerged between treatment duration and PrMN risk, with a median onset of 18.9 months. Risk increased with additional therapy lines: 0.52% (first), 4.2% (second), 1.8% (third), 10.8% (fourth), and 12.2% (>fourth lines). Among PrMN cases, 4 achieved remission, 4 had partial responses, 8 progressed, and 37 died. While this survey is meant as hypotheses-generating, PrMN represent a rare but clinically relevant complication, particularly uncommon when PARPi are administered as first-line therapy. Their occurrence does not appear to be associated with the specific PARPi used or with BRCA mutation status. Early detection, monitoring, and identification of predictive factors are crucial as ovarian cancer outcomes improve and treatment exposure increases.

Lymph node staging in grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

Verification of the prognostic precision of the new 2023 FIGO staging system in endometrial cancer patients – An international pooled analysis of three ESGO accredited centres

Recently, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer (EC) critically integrating new pathological and molecular features was published. The present study evaluated the clinical impact of the new 2023 FIGO staging system by comparing it to the previous 2009 system. This is an international, pooled retrospective study of 519 EC patients who underwent primary treatment (and molecular characterisation) at three European Society of Gynaecological Oncology (ESGO) accredited centres in Austria/Italy. Patients were categorised according to the 2009 and the 2023 FIGO staging systems. Stage shifts were analysed and (sub)stage specific 5-year progression-free (PFS) and overall survival (OS) rates were calculated and compared. Different statistical tests were applied to evaluate the prognostic precision of the two FIGO staging systems and to compare them to each other. (Sub)stage shifts occurred in 143/519 (27.6%) patients: 123 upshifts (23.7%) and 20 (3.9%) downshifts. 2023 FIGO staging system identified a stage I cohort with a notably higher 5-year PFS rate compared to 2009 (93.0% versus 87.4%, respectively). For stage II disease, the 5-year PFS rate was similar in the 2023 and the 2009 FIGO staging systems (70.2% versus 71.2%, respectively). The two new molecularly defined 2023 FIGO substages IAm The new 2023 FIGO stating system led to a substantial stage shift in about one quarter of patients leading to a higher prognostic precision. In early stage disease, the new substages added further prognostic granularity and identified treatment relevant subgroups.

Natural language processing as consultation service platform or clinical decision support system in gynecologic oncology: a systematic review.

Natural language processing is emerging as a key application of artificial intelligence in oncology. This systematic review aims to evaluate the performance and methodological frameworks of natural language processing systems in gynecologic oncology. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. MEDLINE, EMBASE, and Web of Science were searched for studies published between January 2015 and February 2025. Outcomes were synthesized across 3 research questions: the accuracy of natural language processing systems used as consultation service platforms; the accuracy of natural language processing systems used as clinical decision support systems; and the benchmarking methodologies applied, including their associated methodological outcomes. Consultation service platforms deliver general medical information, whereas clinical decision support systems provide recommendations that are integrated into the patient's clinical workflow. This review analyzed 12 retrospective studies. Consultation service platforms were less accurate than clinicians (60% vs 86.7%) and rated lower in response quality (2.96/5 vs 4.2/5) but outperformed guideline-based answers (1.54/2 vs 1.38/2). In cervical cancer, ChatGPT surpassed experts (7.0 vs 6.1). ChatGPT-4 showed a concordance of 70% with the National Comprehensive Cancer Network and 60% with the European Society of Gynaecological Oncology guidelines in clinical decision support tasks, with an overall recommendation accuracy of 75%. IBM Watson achieved a 72.8% concordance with guidelines. Prompting was applied from 100% to 37.5% across studies. Qualitative benchmarking varied across studies: 83.3% used clinical guidelines and 37.5% of consultation service platforms studies used expert answers. Four- or 5-point scales and binary scoring were used to assess consultation service platforms and clinical decision support systems, respectively. Clinicians remain superior in complex reasoning, but natural language processing systems demonstrate robust performance in guideline-driven tasks, with advantages in speed, readability, and reproducibility. However, performance declined in nuanced scenarios and among under-represented patient sub-groups. Large language models currently play a supportive rather than substitutive role in gynecologic oncology.

Evaluation of decision regret and reproductive concerns following fertility-sparing treatment in adolescents and young adults with atypical endometrial hyperplasia or endometrioid endometrial cancer-a single-center cross-sectional study.

To examine decision regret and reproductive concerns following fertility-sparing treatment in adolescents and young adults (defined as aged 15-39 years) with endometrial atypical hyperplasia or endometrioid endometrial cancer. All adolescents and young adults diagnosed with endometrial atypical hyperplasia or endometrioid endometrial cancer between January 1, 2021, and December 31, 2023, who underwent fertility-sparing treatment at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS hospital in Rome, Italy, were contacted. Patients were asked to fill out the 5-item Decision Regret Scale score and the 18-item Reproductive Concerns After Cancer score, assessing the following areas of concern: fertility potential, partner disclosure of fertility status, child's health, personal health, acceptance of possible infertility, and becoming pregnant. Thirty-two patients gave informed consent and were included. Complete treatment response was achieved in 93.9% of cases, whereas among those with endometrioid endometrial cancer the complete response rate was 100.0%. After a median follow-up of 29 months (range; 11-44 months), 1 patient (3.1%) experienced persistent disease and 6 patients (18.8%) had a relapse. Five patients (15.6%) underwent hysterectomy. Among the 20 patients who tried to conceive following diagnosis, a total of 12 pregnancies were achieved in 11 patients (pregnancy rate 60.0%). The live birth rate per pregnancy was 66.7%; 2 pregnancies were still ongoing. Mean Decision Regret Scale score was 16.6 (SD 24.0, range; 0-100). Mean Reproductive Concerns After Cancer score for all items was 2.78 (SD 1.17, range; 1-5), with greatest concern for acceptance of possible infertility (mean 3.23, SD 1.08), fertility potential (mean 3.12, SD 1.24) and child's health (mean 3.02, SD 1.31). Regardless favorable oncological and obstetrical outcomes and mild decision regret, reproductive concerns are common following fertility-sparing treatment in adolescents and young adults with endometrial atypical hyperplasia or endometrioid endometrial cancer.

Olaparib dose reduction in BRCA-mutated platinum-sensitive ovarian cancer recurrence: real-world data.

The poly (adenosine diphosphate-ribose) polymerase inhibitor olaparib has demonstrated significant efficacy in treating patients with BRCA-mutated patients with ovarian cancer. However, adverse events, particularly hematologic toxicities, often necessitate dose reduction or treatment interruption. Our study investigates the survival outcomes associated with olaparib dose reduction in patients with recurrent ovarian cancer in a real-world setting. We conducted a retrospective analysis on patients with BRCA-mutated ovarian cancer treated with olaparib in a recurrent setting from 2019 to 2022. Patients were categorized based on dose-reduction status: no reduction (olaparib 600 mg; group 1), dose reduction level 1 (olaparib 500 mg; group 2), and dose reduction level 2 (olaparib 400 mg; group 3). These dose levels were selected by current guideline-based protocols for olaparib dose modification. Primary endpoints were progression-free survival and overall survival, while secondary endpoints included comparing the reduction rates and safety between the 3 groups. Eighty-seven patients were included, with 45 (52%) receiving dose reduction. The median progression-free survival for patients on standard dose was 27 months, compared to 28 and 32 months for groups 2 and 3, respectively (HR 1.587, 95% CI 0.673 to 2.744, p = .323). The median overall survival was 44 months for group 1, 52 for group 2, and 43 for group 3 (HR 0.737, 95% CI 0.413 to 1.317, p = .296). Grade ≥3 adverse events occurred in 2 patients (4.7%) of group 1, leading to a dose interruption without a reduction. Fatigue (n = 15; 35.7%) and nausea (n = 14; 33.3%) have often been reported in patients on the standard dose group. In our cohort, olaparib dose reduction did not adversely affect oncological outcomes in patients with recurrent ovarian cancer. These results suggest that a reduced dosing strategy is a viable option in patients experiencing treatment-related adverse events. However, these findings should be confirmed in larger clinical data.

Detection of Peritoneal Metastases by Diagnostic LAparoscopy in Patients With Locally Advanced Cervical Carcinoma

The study hypothesizes that specific subgroups of LACC patients, (AJCC stage T3/T4, grade 3 tumors, and para-aortic lymph node involvement), have a higher prevalence of peritoneal metastasis. This peritoneal spread may serve as a prognostic factor, and diagnostic laparoscopy could improve staging accuracy, thereby guiding personalized treatment strategies and improving oncological outcomes.

Robotic-assisted Versus Conventional Laparoscopic Surgery in Obese Patients With Early Endometrial Cancer

Data across literature suggest that robotic surgery may offer benefit specifically in patient with morbid obesity with endometrial cancer, but to date no randomized trials have been conducted to confirm these observations. This randomized controlled multicentric trial aims to evaluate the most appropriate minimally invasive surgical approach in morbidly obese (BMI \>= 30) patients with endometrial carcinoma.

Prospective Validation of the ADNEX Model for Discrimination Between Benign and Malignant Adnexal Masses in Pregnancy: International Ovarian Tumour Analysis in Pregnancy Study (p-IOTA)

Prospective Validation of the ADNEX Model for discrimination between benign and malignant adnexal masses in pregnancy: International Ovarian Tumour Analysis in pregnancy study (p-IOTA)

NUVOLA TRIAL Open-label Multicentre Study

Around 15-25% of ovarian cancer (OC) patients carry germ-line mutation in BRCA1 or BRCA2 genes. Recent evidences showed that OC women with germline BRCA1/2 mutations (gBRCAmut) have an improved survival and higher platinum-sensitivity compared to BRCA1/2 naive (BRCAwt). Interestingly, disease appearance in BRCAmut women is more diffuse than in BRCAwt cases, with significantly higher peritoneal tumour load. Nonetheless, BRCAmut women additionally show a higher benefit of platinum-based neoadjuvant chemotherapy (NACT) plus interval debulking surgery compared with BRCAwt women in terms of clinical and pathological responses, suggesting that BRCA mutational status might be used as a molecular tool to personalize treatment in high-grade serous ovarian cancer (HGSOC) patients. OLAPARIB in BRCA mutation carriers Olaparib is a potent oral poly (ADP-ribose) polymerase (PARP) inhibitor that causes synthetic lethality in BRCA1/2-deficient tumour cells. In patients with platinum-sensitive relapsed serous ovarian cancer, olaparib maintenance treatment significantly improved the duration of progression-free survival compared with placebo (hazard ratio \[HR\] 0.35 \[95% CI (confidence interval) 0.25-0.49\]; p\<0.0001), with the greatest clinical benefit in patients with BRCA mutations (HR 0.18 \[95% CI 0.10-0.31\]; p\<0.0001). Preclinical data suggest that olaparib might also potentiate the efficacy of DNA-damaging chemotherapies, including platinum-containing drugs such as carboplatin. In a recent phase Ib/II study, olaparib plus weekly carboplatin and paclitaxel in relapsed ovarian cancer patients was shown to be safe, well tolerated and effective, especially in germline BRCA mutated (gBRCAmut) patients. Possibly, the addition of a PARP inhibitor (olaparib) to NACT in HGSOC patient with germline or somatic BRCA1/2 mutation is able to increase the pathological complete response rate to conventional chemotherapy. Combination of intermittent olaparib with weekly carboplatin and paclitaxel might achieve a higher pathological response rate, with an acceptable toxicity profile.

Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) in Ovarian Cancer Recurrence

The purpose of this study is to determine the role of surgery followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) versus surgery alone in patients with platinum-sensitive first recurrence of ovarian cancer. Moreover it is a prospective randomized multicenter trial, aimed to investigate the prognostic role of surgery plus HIPEC versus surgery alone in terms of progression free interval, overall survival, morbidity and mortality, second recurrence pattern, quality of life with EORTC QLQ-C30 and QLQ OV28 questionnaires.

Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm

Patients with advanced ovarian cancer (FIGO stage III C) and highly disseminated tumor will be randomized into two arms: primary debulking surgery followed by adjuvant chemotherapy vs. neoadjuvant chemotherapy followed by interval debulking surgery (IDS). The primary end point is the evaluation and comparison of the surgical complications of primary surgery and IDS and the evaluation of the progression free survival (PFS)